ArticleBlood2022
Excess heme upregulates heme oxygenase 1 and promotes cardiac ferroptosis in mice with sickle cell disease.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.
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Who cites it
111 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.
- Ferroptosis and ferritinophagy in diabetes complications.Molecular metabolism · 2022Pooled it
- Quercetin Alleviates Ferroptosis-Induced Renal Fibrosis by Modulating the PRDM9/HMOX1/PTGS2 Axis.ACS omega · 2026Article
- Engineered exosomes encapsulated miR-218-5p alleviate the progression of PMRedox biology · 2026Article
- HMOX1 controls a heme-ferritin switch that protects cells from ferroptosis.Science advances · 2026Article
- Blood-brain barrier-penetrant nanotherapy inhibits haem oxygenase-1-mediated ferroptosis for post-resuscitation neuroprotection.Nature communications · 2026Article
- Heme acts as a metabolic brake on erebosis in the Drosophila gut.PLoS biology · 2026Article
- The biphasic interactions between ferroptosis and oxidative stress: from molecular mechanisms to disease interventions.Molecular biology reports · 2026Review
- Sickle cell disease-associated pulmonary hypertension: an integrated framework linking pathologies, mechanisms, and clinical phenotypes.EBioMedicine · 2026Review
- Effects of Extreme Heat Exposure on Heatstroke and Liver Injury in Mice: The Role of PPARα.Environmental health perspectives · 2026Article
- Biomimetic β-lapachone and hemin nanoassembly for intracellular oxidation cascade amplified ferroptosis in hepatocellular carcinoma therapy.Journal of nanobiotechnology · 2026Article
- Modular nanotherapeutics with spatiotemporal precision for phase-specific treatment of intracerebral hemorrhage.Bioactive materials · 2026Article
- Development and validation of programmed cell death related genes in intracranial aneurysms.BMC neurology · 2026Article
- ERM Inhibition Confers Ferroptosis Resistance through ROS-Induced NRF2 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- STING synergizes with TOX suppressing HO-1 expression to trigger ferroptosis in tumor-infiltrating CD8+ T cell and immunotherapy resistance.Nature communications · 2026Article
- A novel transdermal curcumin gel shows potential in improving cardiac bioenergetic functions in Berkeley sickle cell mice.Blood vessels, thrombosis & hemostasis · 2026Article
- NAT10-Mediated ac4C-Modification Exacerbates Ferroptosis by Stabilizing HMOX1 in Deep Vein Thrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Sustained expression of hemopexin in an animal model of sickle cell anemia.Blood vessels, thrombosis & hemostasis · 2026Article
- TIM-4International journal of biological sciences · 2026Article
- Fueling Death: The Metabolic Control of Ferroptosis.Advances in experimental medicine and biology · 2026Review
- The mechanisms by which free heme exacerbates sepsis and the potential therapeutic targets.Frontiers in immunology · 2026Review
51 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Sickle cell disease (SCD) is characterized by increased hemolysis, which results in plasma heme overload and ultimately cardiovascular complications. Here, we hypothesized that increased heme in SCD causes upregulation of heme oxygenase 1 (Hmox1), which consequently drives cardiomyopathy through ferroptosis, an iron-dependent non-apoptotic form of cell death. First, we demonstrated that the Townes SCD mice had higher levels of hemopexin-free heme in the serum and increased cardiomyopathy, which was corrected by hemopexin supplementation. Cardiomyopathy in SCD mice was associated with upregulation of cardiac Hmox1, and inhibition or induction of Hmox1 improved or worsened cardiac damage, respectively. Because free iron, a product of heme degradation through Hmox1, has been implicated in toxicities including ferroptosis, we evaluated the downstream effects of elevated heme in SCD. Consistent with Hmox1 upregulation and iron overload, levels of lipid peroxidation and ferroptotic markers increased in SCD mice, which were corrected by hemopexin administration. Moreover, ferroptosis inhibitors decreased cardiomyopathy, whereas a ferroptosis inducer erastin exacerbated cardiac damage in SCD and induced cardiac ferroptosis in nonsickling mice. Finally, inhibition or induction of Hmox1 decreased or increased cardiac ferroptosis in SCD mice, respectively. Together, our results identify ferroptosis as a key mechanism of cardiomyopathy in SCD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.